Course: CBE447
Instructor: Brynildsen
S 2016

Description of Course Goals and Curriculum

The curriculum for this course is split in two: the first half of the semester gives a broad overview of biochemistry and metabolic engineering suitable for any student in the natural sciences or engineering to understand the field.  This half of the class ends with a standard in-class midterm examination.  The second half of the semester is spent reviewing research articles, essentially studying how metabolic engineers (and scientists in general) approach questions in research.  To demonstrate understanding of research methodology, the final project is a 10-page research proposal.  This section of the course also includes frequent debates and guest speakers from industry and academia.

The goal of the course, then, is twofold.  First, to give students a fundamental understanding of metabolic engineering, and second, to elucidate the research process through the lens of metabolic engineering.

Learning From Classroom Instruction

The first half of the course is devoted to teaching two main topics: firstly, the fundamentals of biochemistry (glycolysis, the TCA cycle, and the pentose phosphate pathway among others).  An example midterm problem testing this content would be filling in the names of the enzymes in a metabolic pathway (in order).  This content is essentially straightforward memorization, and is important for the second half of the course.  If an assigned article talks about replacing enzymes in glycolysis, it is very helpful to have a holistic understanding of the process of glycolysis, rather than having to look everything up.  Fortunately, there is not too much information to memorize.

The second major topic is methods in metabolic engineering (such as gene knockout strategies, laboratory techniques, computer simulation methods, and some mathematical analysis).  Understanding how different laboratory techniques work - such as western blot, qPCR, restriction digest, etc. - is very important for reading papers and later for writing your own proposal.  While this content has more of a math focus, it does not require much practice for anyone with a basic calculus background (around 104, along with some familiarity with matrices)

This gives students a good background for the second half of the course, which consists primarily of literature review: two research papers are assigned for reading each class meeting, and every class consists of a discussion of how the paper approaches its research questions: the authors’ logic, methodology, error analysis, strengths and weaknesses, and the overall scientific merit of the paper.

Learning For and From Assignments

As mentioned in the previous section, the main assignments for this course are readings from the scientific literature.  The course is graded based on the midterm, class participation (including discussion and debates), and the final proposal.  Thus, to do well in the course, it is essential to understand good scientific reasoning.  The best way to develop this is in the classroom discussions about each article.  Critical reading beforehand will help - the author’s scientific reasoning, including the assumptions and implications that the authors make about their results; their error analysis; and the strength of their conclusions are all common topics that come up in discussion.  Learning to read with an eye to these will be helpful in developing your abilities in scientific inquiry, which is essential to writing the final proposal.  In the same vein, Prof. Brynildsen hosts two debates during the semester, in which two teams of students read the same article and argue either for or against its scientific merit and publication in a journal.  The same theme of critical reading applies here.

For the final proposal, students are required to come up with their own research topic and expand upon their methodology; for example, engineering E. coli to produce a certain pharmaceutical.  Students will need to understand the metabolic pathways involved and the laboratory techniques to carry out the project.  Prof. Brynildsen meets with all students two or three times during the semester to narrow topics and offer critique at different stages: these meetings are very helpful, and he is always willing to meet or offer advice at other times.

External Resources

Supplementary reading is included on the Blackboard site as well as a few textbooks, but a textbook is not particularly useful for the first half of the course, except perhaps as a reference - none of the material is covered in enough detail to necessitate one.

For the final project, ecocyc.org and biocyc.org are very useful for learning more about the enzymes and pathways involved in your proposal.  Web of Science (if you Google that term, this is the first result) is helpful for finding papers: it allows you to see the articles cited in a given paper; the articles in which it is cited; and the impact factor of each journal, which gives you an idea of its overall significance.

What Students Should Know About This Course For Purposes Of Course Selection

This course counts as an elective in the biology track of CBE (as well as a 400-level CBE course, which is a general requirement for CBE graduation).

Metabolic Engineering

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